| RRC ID |
87642
|
| Author |
Saied-Santiago K, Baxter M, Mathiaparanam J, Granato M.
|
| Title |
Serotonin neuromodulation directs optic nerve regeneration.
|
| Journal |
Development
|
| Abstract |
Optic nerve (ON) regeneration in mammalian systems is limited by an overshadowing dominance of inhibitory factors. This has severely hampered the identification of pro-regenerative pathways. Here, we take advantage of the regenerative capacity of larval zebrafish to identify pathways that promote ON regeneration. From a small molecule screen, we identified modulators of serotonin (5-HT) signaling that inhibit ON regeneration. We find that several serotonin type-1 (5-HT1) receptor genes are expressed in retinal ganglion cells during regeneration and that inhibiting 5-HT1 receptors or components of the 5-HT pathway selectively impedes ON regeneration. We show that 5-HT1 receptor signaling is dispensable during ON development yet is required for regenerating axons to emerge from the injury site. Blocking 5-HT receptors once ON axons have crossed the chiasm does not inhibit regeneration, suggesting a selective role for 5-HT receptor signaling early during ON regeneration. Finally, we show that agonist-mediated activation of 5-HT1 receptors leads to enhanced and ectopic axonal regrowth. Combined, our results provide evidence for mechanisms through which serotonin-dependent neuromodulation directs ON regeneration in vivo.
|
| Volume |
152(13)
|
| Published |
2025-7-1
|
| DOI |
10.1242/dev.204334
|
| PII |
368298
|
| PMID |
40521655
|
| PMC |
PMC12276806
|
| MeSH |
Animals
Axons / metabolism
Axons / physiology
Nerve Regeneration* / drug effects
Nerve Regeneration* / physiology
Optic Nerve* / drug effects
Optic Nerve* / physiology
Optic Nerve Injuries
Receptors, Serotonin, 5-HT1 / genetics
Receptors, Serotonin, 5-HT1 / metabolism
Retinal Ganglion Cells / metabolism
Serotonin* / metabolism
Signal Transduction / drug effects
Zebrafish / physiology
Zebrafish Proteins / genetics
Zebrafish Proteins / metabolism
|
| IF |
5.611
|
| Resource |
| Zebrafish |
Tol-056 |
